Oxytocin Enhances Amygdala-Dependent, Socially Reinforced Learning and Emotional Empathy in Humans

Oxytocin (OT) is becoming increasingly established as a prosocial neuropeptide in humans with therapeutic potential in treatment of social, cognitive, and mood disorders. However, the potential of OT as a general facilitator of human learning and empathy is unclear. The current double-blind experiments on healthy adult male volunteers investigated first whether treatment with intranasal OT enhanced learning performance on a feedback-guided item–category association task where either social (smiling and angry faces) or nonsocial (green and red lights) reinforcers were used, and second whether it increased either cognitive or emotional empathy measured by the Multifaceted Empathy Test. Further experiments investigated whether OT-sensitive behavioral components required a normal functional amygdala. Results in control groups showed that learning performance was improved when social rather than nonsocial reinforcement was used. Intranasal OT potentiated this social reinforcement advantage and greatly increased emotional, but not cognitive, empathy in response to both positive and negative valence stimuli. Interestingly, after OT treatment, emotional empathy responses in men were raised to levels similar to those found in untreated women. Two patients with selective bilateral damage to the amygdala (monozygotic twins with congenital Urbach–Wiethe disease) were impaired on both OT-sensitive aspects of these learning and empathy tasks, but performed normally on nonsocially reinforced learning and cognitive empathy. Overall these findings provide the first demonstration that OT can facilitate amygdala-dependent, socially reinforced learning and emotional empathy in men.

[1]  M. Trimble,et al.  The Human Amygdala , 2010 .

[2]  Sabine C. Herpertz,et al.  Effects of intranasal oxytocin on emotional face processing in women , 2010, Psychoneuroendocrinology.

[3]  Oliver P. John,et al.  Oxytocin receptor genetic variation relates to empathy and stress reactivity in humans , 2009, Proceedings of the National Academy of Sciences.

[4]  W. Young,et al.  Oxytocin: The great facilitator of life , 2009, Progress in Neurobiology.

[5]  René Hurlemann,et al.  Reduced 5-HT(2A) receptor signaling following selective bilateral amygdala damage. , 2009, Social cognitive and affective neuroscience.

[6]  U. Habel,et al.  Generalized deficit in all core components of empathy in schizophrenia , 2009, Schizophrenia Research.

[7]  Peter Klaver,et al.  Oxytocin Makes a Face in Memory Familiar , 2009, The Journal of Neuroscience.

[8]  R. Adolphs,et al.  The social brain: neural basis of social knowledge. , 2009, Annual review of psychology.

[9]  Geoffrey Bird,et al.  Effects of Oxytocin and Prosocial Behavior on Brain Responses to Direct and Vicariously Experienced Pain , 2008, Emotion.

[10]  Philip B. Mitchell,et al.  Oxytocin Enhances the Encoding of Positive Social Memories in Humans , 2008, Biological Psychiatry.

[11]  Raffael Kalisch,et al.  Oxytocin Attenuates Affective Evaluations of Conditioned Faces and Amygdala Activity , 2008, The Journal of Neuroscience.

[12]  U. Fischbacher,et al.  Oxytocin Shapes the Neural Circuitry of Trust and Trust Adaptation in Humans , 2008, Neuron.

[13]  A. Schulz,et al.  Post-learning intranasal oxytocin modulates human memory for facial identity , 2008, Psychoneuroendocrinology.

[14]  Tania Singer,et al.  University of Zurich Zurich Open Repository and Archive I Feel How You Feel but Not Always: the Empathic Brain and Its I Feel How You Feel but Not Always: the Empathic Brain and Its Modulation , 2009 .

[15]  Oliver T Wolf,et al.  Dissociation of Cognitive and Emotional Empathy in Adults with Asperger Syndrome Using the Multifaceted Empathy Test (MET) , 2008, Journal of autism and developmental disorders.

[16]  Philip B. Mitchell,et al.  Oxytocin Increases Gaze to the Eye Region of Human Faces , 2008, Biological Psychiatry.

[17]  Michael Wagner,et al.  Amygdala control of emotion-induced forgetting and remembering: Evidence from Urbach-Wiethe disease , 2007, Neuropsychologia.

[18]  Laura G. Kirsch,et al.  Emotional deficits in psychopathy and sexual sadism: implications for violent and sadistic behavior. , 2007, Clinical psychology review.

[19]  Christian Büchel,et al.  Oxytocin Attenuates Amygdala Responses to Emotional Faces Regardless of Valence , 2007, Biological Psychiatry.

[20]  P. Zak,et al.  Oxytocin Increases Generosity in Humans , 2007, PloS one.

[21]  J. McGrath,et al.  The molecular basis of lipoid proteinosis: mutations in extracellular matrix protein 1 , 2007, Experimental dermatology.

[22]  I. McGregor,et al.  A role for oxytocin and 5-HT1A receptors in the prosocial effects of 3,4 methylenedioxymethamphetamine (“ecstasy”) , 2007, Neuroscience.

[23]  Oliver T Wolf,et al.  Who Cares? Revisiting Empathy in Asperger Syndrome , 2007, Journal of autism and developmental disorders.

[24]  S. Herpertz,et al.  Oxytocin Improves “Mind-Reading” in Humans , 2007, Biological Psychiatry.

[25]  Larry J. Young,et al.  Neuropeptidergic regulation of affiliative behavior and social bonding in animals , 2006, Hormones and Behavior.

[26]  F. Cendes,et al.  Amygdalae Calcifications Associated with Disease Duration in Lipoid Proteinosis , 2006, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[27]  Peter Kirsch,et al.  Oxytocin Modulates Neural Circuitry for Social Cognition and Fear in Humans , 2005, The Journal of Neuroscience.

[28]  Jon R. Webb,et al.  Gender Differences in the Relationship Between Empathy and Forgiveness , 2005, The Journal of social psychology.

[29]  U. Fischbacher,et al.  Oxytocin increases trust in humans , 2005, Nature.

[30]  P. Veinante,et al.  Vasopressin and Oxytocin Excite Distinct Neuronal Populations in the Central Amygdala , 2005, Science.

[31]  Daniel Tranel,et al.  Amygdala damage impairs emotional memory for gist but not details of complex stimuli , 2005, Nature Neuroscience.

[32]  P. Schyns,et al.  A mechanism for impaired fear recognition after amygdala damage , 2005, Nature.

[33]  D. Hellhammer,et al.  Selective amnesic effects of oxytocin on human memory , 2004, Physiology & Behavior.

[34]  Long-chuan Yu,et al.  Roles of oxytocin in spatial learning and memory in the nucleus basalis of Meynert in rats , 2004, Regulatory Peptides.

[35]  R. Dantzer,et al.  Modulation of social memory in male rats by neurohypophyseal peptides , 1987, Psychopharmacology.

[36]  C. Kirschbaum,et al.  Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress , 2003, Biological Psychiatry.

[37]  R. Dolan,et al.  An emotion-induced retrograde amnesia in humans is amygdala- and β-adrenergic-dependent , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[38]  R. Blair,et al.  Facial expressions, their communicatory functions and neuro-cognitive substrates. , 2003, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[39]  小羽 俊士,et al.  Wisconsin card sorting test , 2013 .

[40]  Jan Born,et al.  Sniffing neuropeptides: a transnasal approach to the human brain , 2002, Nature Neuroscience.

[41]  David I. Perrett,et al.  Facial expressions of emotion: Stimuli and tests (FEEST) , 2002 .

[42]  T. Insel,et al.  Oxytocin in the Medial Amygdala is Essential for Social Recognition in the Mouse , 2001, The Journal of Neuroscience.

[43]  A. Anderson,et al.  Lesions of the human amygdala impair enhanced perception of emotionally salient events , 2001, Nature.

[44]  J. Ridley Studies of Interference in Serial Verbal Reactions , 2001 .

[45]  John A Updegraff,et al.  Biobehavioral responses to stress in females: tend-and-befriend, not fight-or-flight. , 2000, Psychological review.

[46]  E. Bullmore,et al.  Social intelligence in the normal and autistic brain: an fMRI study , 1999, The European journal of neuroscience.

[47]  S. Wise,et al.  Role of the Hippocampal System in Conditional Motor Learning: Mapping Antecedents to Action , 1999, Hippocampus.

[48]  R. Adolphs,et al.  The human amygdala in social judgment , 1998, Nature.

[49]  P. Veinante,et al.  Distribution of oxytocin‐ and vasopressin‐binding sites in the rat extended amygdala: a histoautoradiographic study , 1997, The Journal of comparative neurology.

[50]  James L. McGaugh,et al.  The amygdala and emotional memory , 1995, Nature.

[51]  R. Adolphs,et al.  Impaired recognition of emotion in facial expressions following bilateral damage to the human amygdala , 1994, Nature.

[52]  M. Tohyama,et al.  Localization of oxytocin receptor messenger ribonucleic acid in the rat brain. , 1993, Endocrinology.

[53]  T. Insel,et al.  Oxytocin Receptor Distribution Reflects Social Organization in Monogamous and Polygamous Voles , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[54]  J. M. Ree,et al.  Effect of a single dose of des-glycinamide-[Arg8]vasopressin or oxytocin on cognitive processes in young healthy subjects , 1992, Peptides.

[55]  E. Keverne,et al.  Cerebrospinal fluid and plasma concentrations of oxytocin and vasopressin during parturition and vaginocervical stimulation in the sheep , 1991, Brain Research Bulletin.

[56]  B. A. Baldwin,et al.  Intracerebroventricular oxytocin stimulates maternal behaviour in the sheep. , 1987, Neuroendocrinology.

[57]  Malkit Singh,et al.  Lipoid Proteinosis. , 1987, Indian journal of dermatology, venereology and leprology.

[58]  J. Born,et al.  Human memory and neurohypophyseal hormones: Opposite effects of vasopressin and oxytocin , 1984, Psychoneuroendocrinology.

[59]  D. J. Kennett,et al.  Influence of oxytocin on human memory processes. , 1980, Life sciences.

[60]  D. De Wled,et al.  The influence of the posterior and inter-mediate lobe of the pituitary and pituitary peptides on the maintenance of a conditioned avoidance response in rats , 1965 .

[61]  R. Zajonc SOCIAL FACILITATION. , 1965, Science.

[62]  D. de Wied,et al.  THE INFLUENCE OF THE POSTERIOR AND INTERMEDIATE LOBE OF THE PITUITARY AND PITUITARY PEPTIDES ON THE MAINTENANCE OF A CONDITIONED AVOIDANCE RESPONSE IN RATS. , 1965, International journal of neuropharmacology.

[63]  M. Hamilton A RATING SCALE FOR DEPRESSION , 1960, Journal of neurology, neurosurgery, and psychiatry.

[64]  P. Rubé,et al.  L’examen Clinique en Psychologie , 1959 .

[65]  M. Hamilton The assessment of anxiety states by rating. , 1959, The British journal of medical psychology.

[66]  R. Reitan The relation of the trail making test to organic brain damage. , 1955, Journal of consulting psychology.

[67]  P. Osterrieth Le test de copie d'une figure complexe , 1944 .

[68]  A. Rey L'examen psychologique dans les cas d'encéphalopathie traumatique. (Les problems.). , 1941 .

[69]  A. Rey Lexamen psychologique : Dans les cas d'encephalopathie traumatique (Les problemes) , 1941 .

[70]  J. F. Dashiell An experimental analysis of some group effects. , 1930 .

[71]  G. S. Gates,et al.  The effect of encouragement and of discouragement upon performance. , 1923 .

[72]  F. Allport The influence of the group upon association and thought. , 1920 .